At present, cancer is the number one cause of death. Occurrence mechanisms, diagnostic methods, and therapeutic methods for cancer have been developed. However, a large number of advanced cancers have not yet been treated under the present circumstances. In order to improve the current situation, it is considered to be necessary to develop a novel early diagnostic method and therapeutic method.
Immunotherapy has long been anticipated as a method for treating cancers, and various attempts have been made regarding such therapy. However, sufficient antitumor effects have not yet been exhibited. Conventionally, immunotherapy for cancers had previously been centered on nonspecific immunotherapy. In recent years, however, it has been clarified that T cells play an important role in tumor rejection in living bodies. As a result, efforts are now focused on the isolation of a T cell-recognizing cancer antigen that is capable of inducing cytotoxic T lymphocytes (CTL) and the determination of an MHC class I-binding epitope.
To date, many cancer antigens have been isolated by the conventional cDNA expression cloning method, using CTL. This method requires the establishment of a cell line from tumor and the establishment of CTL. Thus, it is difficult to isolate a tumor antigen from carcinomas other than melanomas. In addition, in order to enhance the effects of immunotherapy, it is considered that a treatment method involving mixing many peptides is effective. In order to establish such a treatment method, it is necessary to isolate a large number of antigens. Thus, the conventional cDNA expression cloning method is problematic in that it takes enormous manpower and time to isolate even a single antigen.
In 1995, Pfreundschuh et al. in Germany and Old et al. in U.S.A. have reported the SEREX method, which detects a cancer antigen protein recognized by an antibody in the serum of a cancer patient (Serological Identification of Recombinant cDNA Expression Cloning; Proc. Natl. Acad. Sci. USA 92, 11810-11813, 1995). Many tumor antigens have been isolated by this method. Among antigens isolated by this method, antigens such as MAGE-1 or tyrosinase that induce CTL have also been included. Accordingly, it is pointed out that this method is also useful as a method for detecting an antigen recognized by cell-mediated immunity. Moreover, it has been reported that a cancer antigen recognized by the IgG antibody of a patient was isolated by the above-described method (Int. J. Cancer 72, 965-971, 1997; Cancer Res. 58, 1034-1041, 1998; Int. J. Cancer 29, 652-658, 1998; Int. J. Oncol. 14, 703-708, 1999; Cancer Res. 56, 4766-4772, 1996; and Hum. Mol. Genet. 6, 33-39, 1997).